The objective of this project is to gain an understanding of the interaction of transformed cells with the host immune system. In response to a tumor, the immune system mobilizes mechanisms which, paradoxically, turn off not only the specific antitumor resistance but the general immunological reactivity. Although many factors interact in the subversion of immune system, a key role belongs to active suppressor cell (SC). We will study the significance of host SC with emphasis on T suppressor cells (T[unreadable]S[unreadable]) in three mouse tumor models: P815 mastocytoma, B16 melanoma, and virus-induced lymphoma. All three are progressively growing tumors, antigenic for the syngeneic host. The course of the project has been influenced by two unexpected observations. First, it appears that B16 melanoma does not generate cytotoxic cell response in syngeneic hosts--even those hyperimmunized mice that resist live tumor inoculum lack killer cells (this is in contrast to P815 tumor). lt appears that the immnity to B16 is mediated by humoral antibody that develops readily in both tumor-bearing mice (low titers) and immune mice (high titers). We are currently preparing anti-idiotypic antisera againet the B16-specific autologous antibody. Second, the B16 melanoma (a low-metastatic line) does not induce any appreciable immunosuppression in the host (in contrast to highly metastatic P815 tumor). It may be that development of suppressor cells depends on an invasion of lymphoid tissues by the tumor cells. This possibility will be studied using metastatic and low-metastatic B16 tumor lines. (IB)